An insulin-like hybrid consisting of a modified A-domain of human insulin-like growth factor I and the B-chain of insulin.
We have synthesized an insulin-like compound, consisting of the B-chain of bovine insulin and an A-chain corresponding to the A-domain of human insulin-like growth factor-I (IGF-I), in which the isoleucine residue normally present in position 2 of the A-domain of IGF-I has been replaced with glycine. Biological evaluation of the compound indicated that its insulin-like activity (insulin receptor-binding and stimulation of lipogenesis) was 0.2%, and its growth-factor activity (stimulation of thymidine incorporation) was less than 1%, both relative to natural insulin. We conclude that interactions between IleA2 and TyrA19, which are crucial to high biological activity in insulin, are also present in IGF-I, and are equally critical for its biological activity.
Zong
L
L
Department of Biochemistry, Mount Sinai School of Medicine, City University of New York, New York 10029-6574.
Burke
G T
GT
Katsoyannis
P G
PG
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002417:Cattle; D004247:DNA / Q000096:biosynthesis; D004229:Dithiothreitol; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000138:chemical synthesis* / Q000494:pharmacology; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D004247:DNA; D011972:Receptor, Insulin; D004229:Dithiothreitol